Genetic Variant ZNF319:p.Ala423Val (chr16-57996998-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020807.3(ZNF319):c.1268C>T(p.Ala423Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,595,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ZNF319
NM_020807.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

ZNF319 (HGNC:13644): (zinc finger protein 319) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF319 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04626876).

BS2

High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3 link	c.1268C>T	p.Ala423Val	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1	Q9P2F9
ZNF319	NM_001384365.1 link	c.1268C>T	p.Ala423Val	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1 link	c.1268C>T	p.Ala423Val	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1 link	c.1268C>T	p.Ala423Val	missense_variant	Exon 3 of 3		NP_001371296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF319	ENST00000299237.3 link	c.1268C>T	p.Ala423Val	missense_variant	Exon 2 of 2	1	NM_020807.3	ENSP00000299237.2		Q9P2F9

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

146806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000436

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000612

AC:

AN:

244982

Hom.:

AF XY:

0.0000674

AC XY:

AN XY:

133480

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1448898

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

720356

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000365

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.00000681

AC:

AN:

146920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71782

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000218

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000742

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1268C>T (p.A423V) alteration is located in exon 2 (coding exon 1) of the ZNF319 gene. This alteration results from a C to T substitution at nucleotide position 1268, causing the alanine (A) at amino acid position 423 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.58

M_CAP

Benign

0.023

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.82

REVEL

Benign

0.12

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.031

Polyphen

0.73

Vest4

0.085

MVP

0.068

MPC

1.3

ClinPred

0.058

GERP RS

4.2

Varity_R

0.072

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over